BackgroundIrritant contact dermatitis (ICD) is inflammation of the skin typically manifested by erythema, mild edema, and scaling. Irritant contact dermatitis is a nonspecific response of the skin to direct chemical damage that releases mediators of inflammation predominately from epidermal cells. A corrosive agent causes the immediate death of epidermal cells, manifested by chemical burns and cutaneous ulcers. Note the image below.

Chronic irritant contact dermatitis of the hands in an older worker; the condition resulted in early retirement.The hands are the most important sites of irritant contact dermatitis. Irritant contact dermatitis from repeated workplace exposure of the hands to soaps, cleansers, and solvents is the source of most occupational skin disorders.

Irritant contact dermatitis remains understudied compared with allergic contact dermatitis. Most articles on contact dermatitis concern allergic contact dermatitis. This largely reflects the fact that with history and patch testing, a specific hypersensitivity and a probable cause of dermatitis can be identified in most cases of allergic contact dermatitis.

No diagnostic test exists for irritant contact dermatitis. The diagnosis rests on the exclusion of other cutaneous diseases (especially allergic contact dermatitis) and on the clinical appearance of dermatitis at a site sufficiently exposed to a known cutaneous irritant. Laboratory studies may be of value in eliminating some disorders from the differential diagnosis. (See Workup).

The definitive treatment of irritant contact dermatitis is the identification and removal of any potential causal agents. Advise individuals to use ceramides creams or bland emollients after washing hands with soap and before sleep. (See Treatment.)

Although the term hypoallergenic is used widely in the marketing of consumer products, no Food and Drug Administration–approved definition of "hypoallergenic" exists. Individuals with susceptible skin (eg, atopic dermatitis, facial skin of individuals with rosacea) would benefit greatly from hypoirritating cleansers, cosmetics, moisturizers, and protectants, but there is no standard method for identifying such products.

Go to Allergic Contact Dermatitis, Pediatric Contact Dermatitis, and Protein Contact Dermatitis for complete information on these topics.

PathophysiologyIrritant contact dermatitis is the clinical result of sufficient inflammation

arising from the release of proinflammatory cytokines from skin cells (principally keratinocytes), usually in response to chemical stimuli. Different clinical forms may arise. The 3 main pathophysiological changes are skin barrier disruption, epidermal cellular changes, and cytokine release.

With sufficient concentration or duration of exposures, a wide range of chemicals can act as cutaneous irritants. Common cutaneous irritants include solvents, microtrauma, and mechanical irritants.

Cumulative irritant contact dermatitis from repeated mild skin irritation from soap and water is common. For example, hand-washing frequency of more than 35 times per shift was associated strongly with occupational hand dermatitis in intensive care unit workers (odds ratio = 4.13). Similarly, most cases of "homemaker's" eczema are irritant contact dermatitis resulting from repeated skin exposure to low-grade cutaneous irritants, particularly soaps, water, and detergents.

Solvents cause cutaneous irritation because they remove essential fats and oils from the skin, which increases transepidermal water loss and renders the skin susceptible to the increased direct toxic effects of other previously well-tolerated cutaneous exposures. The alcohol propanol is less irritating to the skin than the detergent sodium lauryl sulfate.

p Ka, an acid dissociation constant, is a quantitative measure of the strength of an acid in solution. p Ka has been shown to be highly predictive of acute skin irritation for acids and bases: acids with a p Ka of less than 4 and bases with a p Ka of less than 8 are highly irritative.[1]

Microtrauma may produce skin irritation. A common example is fiberglass, which may produce pruritus with minimal visible inflammation in susceptible individuals. Many plant leaves and stems bear small spicules and barbs that produce direct skin trauma.

Physical irritants (eg, friction, abrasive grains, occlusion) and detergents such as sodium lauryl sulfate produce more irritant contact dermatitis in combination than singly.[2] Propanol and sodium lauryl sulfate are not additive irritants, however.

Skin irritation predisposes the skin to develop sensitization to topical agents. Skin irritation by both nonallergenic and allergenic compounds induces Langerhans cell migration and maturation.[3] An exacerbation of irritant contact dermatitis may reflect development of allergic contact dermatitis to topical creams, medications, or rubber gloves.

The pathogenesis of irritant contact dermatitis involves resident epidermal

cells, dermal fibroblasts, endothelial cells, and various leukocytes interacting with each other under the control of a network of cytokines and lipid mediators. Keratinocytes play an important role in the initiation and perpetuation of skin inflammatory reactions through the release of and responses to cytokines. Resting keratinocytes produce some cytokines constitutively.

A variety of environmental stimuli (eg, ultraviolet light, chemical agents) can induce epidermal keratinocytes to release the following cytokines:

Inflammatory cytokines (interleukin 1, tumor necrosis factor-alpha)Chemotactic cytokines (interleukin 8, interleukin 10)Growth-promoting cytokines (interleukin 6, interleukin 7, interleukin 15,

granulocyte-macrophage colony-stimulating factor, transforming growth factor–alpha)

Cytokines regulating humoral versus cellular immunity (interleukin 10, interleukin 12, interleukin 18)

Intercellular adhesion molecule 1 promotes the infiltration of leukocytes into the epidermis in cutaneous inflammatory reactions, including irritant contact dermatitis.

Significantly increased numbers of dividing keratinocytes are present 48 and 96 hours after exposure to the anionic emulsifying agent sodium lauryl sulfate (used in shampoos, skin cleansers, acne treatments, and toothpastes and in laboratories as an experimental irritant). However, Heinemann et al found that repeated occlusive application of 0.5% sodium lauryl sulfate over 3 weeks often resulted in adaptation (the so-called hardening phenomenon), with an increase in ceramide 1 in the lipid composition of the stratum corneum.[4]

All irritants provoke a similar pattern of cellular infiltration in the dermis; the densities of most of the cell types rise in proportion to the intensity of inflammation. Within the epidermis, marked differences exist in the patterns of cellular infiltration among different irritants.

Individuals with a history of atopic dermatitis are prone to develop irritant contact dermatitis of the hands. Polymorphisms in the filaggrin (FLG) gene, which result in loss of filaggrin production, may alter the skin barrier and are a predisposing factor for atopic dermatitis. FLG null alleles are associated with increased susceptibility to chronic irritant contact dermatitis.[5]

EtiologyAlmost any material may be a cutaneous irritant, if the exposure is sufficiently prolonged and/or the concentration of the substance sufficiently

high. Environmental factors may enhance the effect of other irritants.

Dry air and temperature variation

Dry air renders the skin more susceptible to cutaneous irritants. Sufficiently dry air alone may provoke irritant contact dermatitis. Most cases of winter itch are a result of dry skin from the drier air found during sustained periods of cold weather.

An increase in temperature (up to 43°C from 20°C) increases the cutaneous effect of an irritant.[6]

Water

Continual exposure to water may produce maceration or repeated evaporation of water from the skin may produce cutaneous irritation by desiccation of the skin. Even distilled water experimentally provokes increased CD11c+ cells and neutrophils in the epidermis.

Solvents

Many individuals are exposed to solvents, particularly at work. Solvents such as alcohol or xylene remove lipids from the skin, producing direct irritant contact dermatitis and rendering the skin more susceptible to other cutaneous irritants, such as soap and water.

Irritant contact dermatitis from alcohol most often is cumulative. Manual workers may wash their hands inappropriately with solvents to remove oil, grease, paints, or other materials; thus, they develop irritant contact dermatitis.

Inappropriate skin cleansing is a primary cause of irritant contact dermatitis in the workplace. Washing facilities and methods must be inspected when investigating the workplace for 1 or more cases of occupational irritant contact dermatitis. The irritating agents include aromatic, aliphatic, and chlorinated solvents, as well as solvents such as turpentine, alcohol, esters, and ketones. Some organic solvents produce an immediate erythematous reaction on the skin and remove lipids from the stratum corneum.

Metalworking fluids

Neat oils most commonly produce folliculitis and acne. They may cause irritant contact dermatitis (as well as allergic dermatitis). Water-based metalworking fluids often cause irritant contact dermatitis in exposed workers; surfactants in these fluids are the main culprit.

Cumulative irritant contact dermatitis

This is common in many occupations that often are termed "wet work."

Healthcare workers wash their hands 20-40 times a day, producing cumulative irritant contact dermatitis. Similar exposures occur among individuals who wash hair repeatedly or in cleaners or kitchen workers.

Multiple skin irritants may be additive or synergistic in their effects. Alcohol-based hand-cleansing gels cause less skin irritation than hand washing and therefore are preferred for hand hygiene from the dermatological point of view. An alcohol-based hand-cleansing gel may even decrease, rather than increase, skin irritation after a hand wash, owing to a mechanical partial elimination of the detergent.[7]

Microtrauma

Fiberglass produces direct damage to the skin, usually manifested by pruritus that may result in excoriation and secondary skin damage. Cutaneous irritation primarily is caused by fiberglass with diameters exceeding 4.5 µm.

Controversy surrounds whether individuals with dermatographism are more susceptible to fiberglass dermatitis.

Most workers with irritant contact dermatitis resulting from fiberglass develop hardening, in which they tolerate further cutaneous exposure to fiberglass.

Many plant leaves and stems bear small spicules and barbs that produce direct skin trauma

Mechanical trauma

Pressure produces callus formation. Pounding produces petechia or ecchymosis. Sudden trauma or friction produces blistering in the epidermis. Repeated rubbing or scratching produces lichenification. Sweating and friction appear to be the main cause of dermatitis that appears under soccer shin guards in children.[8]

Rubber gloves

Some rubber gloves may provoke direct cutaneous irritation. Many workers complain of irritation from the powder in rubber gloves.

Remember that gloves compromised by a hole may allow an irritant to enter; occlusion dramatically increases skin damage from the irritant. Occlusion accentuates the effects, good or bad, of topical agents. Kerosene may produce skin changes similar to that of toxic epidermal necrolysis following occluded cutaneous exposure. Excessive amounts of ethylene oxide in surgical sheets also may produce similar changes.

Sodium lauryl sulfate

This chemical is found in some topical medications, particularly acne medications, as well as a range of soaps and shampoos. It is also a classic experimental cutaneous irritant.

Hydrofluoric acid

A hydrofluoric acid burn is a medical emergency. Remember that onset of clinical manifestations may be delayed after the acute exposure (this is crucial to diagnosis). Unfortunately, hydrofluoric acid burns are most frequent on the digits, where the pain is most severe and management is most difficult (see Hydrofluoric Acid Burns).

Alkalies

Skin surfaces normally have an acidic pH, and alkalies (eg, many soaps) produce more irritation than many acids. The "acid mantle" of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. Use of skin cleansing agents, especially synthetic detergents with a pH of approximately 5.5 rather than alkaline pH, may help prevent skin disease.[9]

EpidemiologyUnited States statistics

Irritant contact dermatitis is common in occupations that involve repeated hand washing or repeated exposure of the skin to water, food materials, and other irritants. High-risk occupations include cleaning, hospital care, food preparation, and hairdressing.

The prevalence of occupational hand dermatitis was found to be 55.6% in 2 intensive care units and was 69.7% in the most highly exposed workers. Hand-washing frequency of more than 35 times per shift was associated strongly with occupational hand dermatitis.[10]

International statistics

In Denmark, cleaners comprise the greatest number of affected workers, but culinary workers have the highest incidence. A higher proportion of prolonged sick leave is seen among those in food-related occupations compared with those in wet occupations.[11]

The incidence rates of contact dermatitis in Germany were 4.5 per 10,000 workers for irritant contact dermatitis, compared with 4.1 per 10,000 workers for allergic contact dermatitis. The highest irritant contact dermatitis annual incidence rates were found in hairdressers (46.9 cases per 10,000 workers per year), bakers (23.5 cases per 10,000 workers per

year), and pastry cooks (16.9 cases per 10,000 workers per year.[12]

Sexual differences in incidence

Irritant contact dermatitis is significantly more common in women than in men. The high frequency of hand eczema in women in comparison with men is caused by environmental factors, not genetic factors.

Occupational irritant contact dermatitis affects women almost twice as often as men, in contrast to other occupational diseases that predominantly affect men. Women are exposed more highly to cutaneous irritants from their disproportionately greater role in housecleaning and the care of small children at home. In addition, women predominantly perform many occupations at high risk for irritant contact dermatitis (eg, hairdressing, nursing).

Age-related differences in incidence

Irritant contact dermatitis may occur at any age. Many cases of diaper dermatitis are irritant contact dermatitis resulting from direct skin irritants present in urine and, especially, feces. Older persons have drier and thinner skin that does not tolerate soaps and solvents as well as younger individuals. Occupational hand eczema often is associated with persistent dermatitis and prolonged sick leave, with substantially greater severity among those with occupational irritant contact dermatitis and atopic dermatitis and age older than 50 years.

PrognosisPrognosis is good for nonatopic individuals in whom irritant contact dermatitis is diagnosed and managed promptly. Individuals with atopic dermatitis remain highly susceptible to irritant contact dermatitis and may find that the tasks of many common occupations (eg, nursing, hairdressing) produce too much direct skin inflammation to continue with these careers.

Hardening may be specific to the irritant inducing the hardening phenomenon and does not occur in all persons exposed long term to an irritant.[1] Hardened skin may also have a thickened stratum granulosum, with changes in the expression of various inflammatory mediators and markers.[1] An induction of an increase in the stratum corneum lipid ceramide 1 may play a key role as a protection mechanism against irritation by repeated application of sodium lauryl sulfate.[2, 4]

Activities of daily living and work may be reduced by severe irritant contact dermatitis.

Acute irritant contact dermatitis reactions to potent irritants (eg, acids,

alkaline solutions) are comparable to a chemical burn and can be graded like thermal burns (ie, first-, second-, or third-degree burns). With appropriate symptomatic management, the prognosis for this type of irritant contact dermatitis is usually good, and, unless the dermis is damaged, no permanent scarring should occur. See Chemical Burns for more information.

Mortality

Hydrofluoric acid is a potent cutaneous irritant used in low-technology and high-technology industries and at home in rust removal.[13] Death from hypocalcemia may ensue if as little as 1% of the skin's surface area is exposed sufficiently to this strong inorganic acid and if complications are not managed optimally (see Hydrofluoric Acid Burns).

Patient EducationRemind individuals that they must continue to avoid cutaneous irritants; they will redevelop or aggravate dermatitis if they continue to have the same skin care exposures that resulted in irritant contact dermatitis. The possibility of secondary or complicating allergic contact dermatitis always must be borne in mind.

For patient education information, see the Skin, Hair, and Nails Center, as well as Contact Dermatitis.

Proceed to Clinical PresentationHistoryA detailed history is required because the diagnosis of irritant contact dermatitis rests on the history of exposure of the affected body site to the cutaneous irritant. Patch testing also is used in severe or persistent cases to exclude allergic contact dermatitis as a component of the individual's cutaneous manifestations.

Onset of symptoms occurs within minutes to hours of exposure in simple acute irritant contact dermatitis. Acute delayed irritant contact dermatitis is characteristic of certain irritants, such as benzalkonium chloride (eg, zephiran, a preservative and disinfectant), which elicits a deferred (8-24 h after exposure) inflammatory reaction.[14]

The onset of signs and symptoms may be delayed by weeks in cumulative irritant contact dermatitis. Cumulative irritant contact dermatitis is a consequence of multiple incidents of subthreshold damage to the skin, with the time between exposures being too short for a full resolution of skin barrier function. Patients with sensitive skin (ie, atopic individuals) have a decreased irritant threshold or a prolonged restoration time, making them more vulnerable to clinical irritant contact dermatitis.

Cumulative irritant contact dermatitis typically occurs with exposure to weak irritants rather than strong ones. Often, the exposure (eg, water) is not only at work but also at home.

These patients report both itching and pain caused by fissuring of the hyperkeratotic skin (chapping). Pain, burning, stinging, or discomfort exceeding pruritus occur early in the clinical course.

Less important subjective criteria for irritant contact dermatitis include the onset of dermatitis within 2 weeks of exposure, and reports of many other coworkers or family members affected.

Occupational history

Irritant contact dermatitis is a major occupational disease; skin disorders comprise up to 40% of occupational illnesses. The physician needs to take an occupational history from adults with suspect irritant contact dermatitis.

Occupational irritant contact dermatitis typically affects workers who are new to a job, who are constitutionally more susceptible to irritant contact dermatitis, or who have not learned to protect their skin from cutaneous irritants. Individuals with history of atopic dermatitis (especially of the hands) are more susceptible to irritant contact dermatitis, particularly of the hands.

Most affected workers have a degree of permanent injury that is lower than that of other occupational diseases; however, the compensation pay was higher for skin diseases than for diseases of the respiratory system or musculoskeletal disorders, according to a study in Denmark.

Physical ExaminationRietschel and Fowler proposed the following as primary diagnostic criteria for irritant contact dermatitis[15] :

Macular erythema, hyperkeratosis, or fissuring predominating over vesiculation

Glazed, parched, or scalded appearance of the epidermisHealing process beginning promptly on withdrawal of exposure to the

offending agentNegative results on patch testing that includes all possible allergensMinor objective criteria for irritant contact dermatitis include the following:

Sharp circumscription of the dermatitisEvidence of gravitational influence such as a dripping effectLower tendency for the dermatitis to spread than in cases of allergic contact

dermatitis

Morphologic changes suggesting small differences in concentration or contact time producing large differences in skin damage

Individuals may develop a habit of continuing to rub a site initially affected by irritant contact dermatitis and may develop secondary neurodermatitis or lichen simplex chronicus (lichenification). This may be accepted as a sequela of an occupational injury.

ComplicationsSkin lesions may become colonized secondarily and/or infected, particularly by Staphylococcus aureus. Secondary neurodermatitis (lichen simplex chronicus) may develop in individuals with irritant contact dermatitis, particularly in those with workplace exposures or under psychological stress.

Postinflammatory hyperpigmentation or hypopigmentation may occur in areas affected by irritant contact dermatitis or persist after resolution of irritant contact dermatitis in individuals with more pigmented skin.

Scarring may occur after corrosive agent exposure, excoriation, or artifact, causing ulceration.

Irritant contact dermatitis increases the risk of sensitization to topical medications.

Proceed to Differential Diagnoses

Diagnostic ConsiderationsOther causes of contact dermatitis must be excluded. Elements of the history and/or patch testing to relevant allergens can identify allergic contact dermatitis. Scabies may resemble fiberglass dermatitis.

Differential DiagnosesAtopic DermatitisDermatologic Manifestations of Renal DiseaseDermatologic Manifestations of ScabiesDrug EruptionsErysipelasErythema Infectiosum (Fifth Disease)Id Reaction (Autoeczematization)Lichen Simplex ChronicusPerioral DermatitisPhytophotodermatitisSeborrheic Dermatitis 

Approach Considerations

No diagnostic test exists for irritant contact dermatitis. The diagnosis rests on the exclusion of other cutaneous diseases (especially allergic contact dermatitis) and on the clinical appearance of dermatitis at a site sufficiently exposed to a known cutaneous irritant. Laboratory studies are generally of little value in proving a diagnosis of contact dermatitis. However, they may be of value in eliminating some disorders from the differential diagnosis.

Findings of significantly elevated serum immunoglobulin E occasionally are useful to substantiate an atopic diathesis in the absence of a personal or family history of atopy.

Go to Allergic Contact Dermatitis, Pediatric Contact Dermatitis, and Protein Contact Dermatitis for complete information on these topics.

Bacterial and Fungal StudiesA bacterial culture can be obtained in cases complicated by secondary bacterial infection. A potassium hydroxide (KOH) examination of scrapings may be performed and samples for mycology may be obtained to exclude superficial tinea infections or candidal infections, depending on site and morphology of lesions.

Patch TestingPatch testing can be performed to diagnose contact allergies, but no patch test exists that proves that a cutaneous irritant is responsible for a particular case of irritant contact dermatitis. Diagnosis rests on exclusion of allergic contact dermatitis and history of sufficient exposure to a cutaneous irritant. Also see the following summaries of clinical guidelines from the Joint Council of Allergy, Asthma and Immunology:

Allergy diagnostic testing: an updated practice parameter. Part 1 [16] Allergy diagnostic testing: an updated practice parameter. Part 2 [17]

Skin BiopsySkin biopsy can help exclude other disorders, such as tinea, psoriasis, or cutaneous T-cell lymphoma. All clinical cases of dermatitis are similar histologically.

Skin biopsy of skin lesions of the palms and soles has several potential pitfalls. The stratum corneum and epidermis are particularly thick there, which makes the histologic diagnosis of psoriasis more difficult and increases the possibility that the specimen lacks sufficient dermis for optimal diagnosis. In the thenar area, an overly deep biopsy can cut the recurrent branch of the median nerve. A biopsy from the sole may leave a chronic painful scar on which the patient must walk. A saucerized shave

biopsy is usually the most suitable method.

Direct MicroscopySkin scrapings of cutaneous lesions may help exclude scabies or may reveal fiberglass fibers as a cause of a patient's pruritus.

Histologic FindingsThe histopathology of acute experimental irritant contact dermatitis has been studied to a greater extent than chronic irritant contact dermatitis, which is the primary clinical complaint. Cellular changes seen in the skin vary according to the chemical nature and concentration of the irritant applied, duration of exposure, severity of ensuing response, and time of sampling for acute irritant contact dermatitis. Many primary irritants cause overt necrosis if applied in a sufficiently high concentration for sufficient time.

Most histologic examinations of irritant contact dermatitis reveal some degree of intercellular edema or spongiosis in the epidermis. Spongiosis usually is less pronounced than that seen in allergic contact dermatitis reactions.

Parakeratosis also is observed widely in irritant contact dermatitis reactions.

The histology of chronic irritant contact dermatitis is one of hyperkeratosis with areas of parakeratosis, moderate-to-marked epidermal hyperplasia (acanthosis), and elongation of the rete ridges.

Proceed to Treatment & Management

Emergency Department CareEmergency department treatment may include the following:

Topical soaks with cool tap water, Burow solution (1:40 dilution), saline (1 tsp/pint)

Lukewarm water baths (antipruritic)Aveeno (oatmeal) lukewarm bathsEmollients (eg, white petrolatum, Eucerin) may be beneficial chronic cases.

Large vesicles may benefit from therapeutic drainage (but not removing the vesicle tops).[1] These lesions should then be covered with antibiotic dressing or a dressing soaked in Burow solution.

Hospital admission is required only in severe cutaneous irritant contact dermatitis, ie, chemical burns from hydrofluoric acid or, occasionally, from freshly mixed Portland cement.

Barrier CreamsCreams containing ceramides (eg, Impruv, Cerave) may be particularly helpful in restoring the epidermal barrier in persons with irritant contact dermatitis and atopic dermatitis. Creams containing dimethicone (eg, Cetaphil cream) can be helpful in restoring the epidermal barrier in persons with wet work–related irritant contact dermatitis.

CleansersMost soaps and detergents are alkaline and induce an increase in cutaneous pH, which affects the physiologic protective acid mantle of the skin by decreasing the fat content. Disruption of stratum corneum and changes in pH are key elements in the induction of irritant contact dermatitis and pruritus by soaps. These conditions are exacerbated in the winter months in patients with dry, sensitive skin.

Syndets, with a pH approximately 5.5, do not modify skin pH. Most bar soaps and liquid detergents available on the market are a mixture of soap and syndet. A study found that Dove and Cetaphil had a lower irritant effect than the other soaps tested. Interestingly, no significant correlation was made between the price of the products and their irritation potential.

Irritant contact dermatitis is a frequent problem in health care workers, due to frequent hand washing. The best antimicrobial efficacy can be achieved with ethanol (60-85%), isopropanol (60-80%), and N -propanol (60-80%). The antimicrobial efficacy of chlorhexidine (2-4%) and triclosan (1-2%) is both lower and slower and carries a potential risk of bacterial resistance.

The use of alcohol-based hand rubs containing various emollients instead of irritating soaps and detergents is one strategy to reduce skin damage, dryness, and irritation in health care workers. Irritant contact dermatitis occurs most frequently with preparations containing 4% chlorhexidine gluconate, less frequently with nonantimicrobial soaps and preparations containing lower concentrations of chlorhexidine gluconate, and least frequently with well-formulated alcohol-based hand rubs containing emollients and other skin conditioners.

Approach ConsiderationsThe definitive treatment of irritant contact dermatitis is the identification and removal of any potential causal agents. An inflammatory reaction from acute delayed irritant contact dermatitis to an agent such as benzalkonium chloride (eg, zephiran) rarely needs treatment and usually resolves with cessation of exposure. Further symptomatic therapy depends on the degree of involvement and the presence or absence of secondary infection.

Advise individuals to use ceramides creams or bland emollients after washing hands with soap and before sleep. Cleansers may be ranked by their irritancy.[18] Recommend mild skin cleansers (eg, Aquanil, Cetaphil cleanser, Oilatum AD, Neutrogena cleanser) in place of soap on affected areas. Instruct individuals to refrain from the use of inappropriate solvents (eg, gasoline) or abrasives (eg, pumice stone) to cleanse hands; these directly defat or traumatize the skin.

A clinical guideline summary from the American Academy of Allergy, Asthma and Immunology, Contact Dermatitis: A Practice Parameter, may be helpful.[19]

Go to Allergic Contact Dermatitis, Pediatric Contact Dermatitis, and Protein Contact Dermatitis for complete information on these topics.

Steroids and ImmunomodulatorsTopical corticosteroids and immunomodulators are of unproven use in treating irritant contact dermatitis. Corticosteroids were found ineffective in treating the surfactant-induced irritant dermatitis when compared with the vehicle and with the untreated control.[20] However, topical steroids may be helpful for superimposed eczematous features.

Potential complications center on the use of steroids, particularly around the eye. The avoidance of long-term steroid use is essential, because such use may cause cataracts, glaucoma, corneal thinning/perforation, and loss of the eye, as well as other problems.

Topical tacrolimus is an irritant that may produce further stinging and irritation in persons with irritant contact dermatitis.[21]

ConsultationsMultidisciplinary consultations may be required when many workers become affected with irritant contact dermatitis in a workplace. Identifying and remediating the causes of widespread irritant contact dermatitis interfering with workplace productivity and worker quality of life is important.

Any patient with hydrofluoric acid burn should be evaluated as a medical emergency by a physician experienced in the management of hydrofluoric exposures and burns. Consider regional intravenous infusion of calcium gluconate as a therapeutic option in hydrofluoric acid burns to forearm, hand, or digits when topical therapy fails.

Proceed to Medication

Medication SummaryAfter the identification and removal of any potential causal agents, the use of ceramides creams or bland emollients and bland barrier creams such as those containing dimethicone are the mainstays of medical treatment for irritant contact dermatitis.

A number of agents commonly found in therapeutic products for the skin (eg, propylene glycol, lactic acid, urea, salicylic acid) may produce further skin inflammation and may need to be avoided in these individuals. Topical corticosteroids play a limited role in the treatment of irritant contact dermatitis. They do not address the process directly, but they may be helpful for superimposed eczematous features.

Corticosteroids, topicalClass Summary

Corticosteroids are immunosuppressives with anti-inflammatory properties that modify the body's immune response to diverse stimuli. Other actions include vasoconstriction and antiproliferation. These agents have limited use in the treatment of irritant contact dermatitis.

View full drug informationAmcinonide 

A highly potent, fluorinated corticosteroid (class 2-3), amcinonide suppresses mitotic activity and causes vasoconstriction. It stimulates synthesis of enzymes needed to decrease inflammation and may suppress histamine release associated with pruritus.

View full drug informationFluocinolone (Capex, Derma-Smoothe/FS) 

Fluocinolone is a fluorinated corticosteroid of mid potency at the 0.025% concentration (class 4-5) and mild potency at the 0.01% concentration (class 6).

Practice Essentials

Individuals with allergic contact dermatitis may have persistent or relapsing dermatitis, particularly if the material(s) to which they are allergic is not identified or if they practice inappropriate skin care. The longer an individual has severe dermatitis, the longer, it is believed, that the dermatitis will take to resolve once the cause is identified.

Essential update: Allergic contact dermatitis caused by non-latex rubber gloves

In a study of surgery personnel in Sweden with occupational allergic contact dermatitis, Pontén et al found evidence that the condition was caused by 1,3-diphenylguanidine (1,3-DPG) in non-latex rubber gloves.[1] Using patch tests, the investigators found that 12 of 16 patients reacted to 1,3-DPG. The 1,3-DPG was present in the gloves worn by the patients in the study, with a higher concentration on the inside of the gloves than on the outside. In 7 of 8 patients, contact allergy to cetylpyridinium chloride was also found[1]

Signs and symptoms

Acute allergic contact dermatitis is characterized by pruritic papules and vesicles on an erythematous base. Lichenified pruritic plaques may indicate a chronic form of the condition.

Individuals with allergic contact dermatitis typically develop the condition within a few days of exposure, in areas that were exposed directly to the allergen. Certain allergens (eg, neomycin), however, penetrate intact skin poorly; in such cases, the onset of dermatitis may be delayed for up to a week following exposure.

Individuals may develop widespread dermatitis from topical medications applied to leg ulcers or from cross-reacting systemic medications administered intravenously.

Intraoral metal contact allergy may result in mucositis that mimics lichen planus, which has an association with intraoral squamous cell carcinoma.

See Clinical Presentation for more detail.

Diagnosis

Diagnostic studies for allergic contact dermatitis include the following:

Potassium hydroxide preparation and/or fungal culture: To exclude tinea; these tests are often indicated for dermatitis of the hands and feet

Patch testing: To identify external chemicals to which the person is allergicRepeat open application test (ROAT): To determine whether a reaction is

significant in individuals who develop weak or 1+ positive reactions to a chemical

Dimethylgloxime test: To determine whether a metallic object contains enough nickel to provoke allergic dermatitis

Skin biopsy: May help to exclude other disorders, particularly tinea, psoriasis, and cutaneous lymphoma

See Workup for more detail.

Management

The definitive treatment for allergic contact dermatitis is the identification and removal of any potential causal agents; otherwise, the patient is at increased risk for chronic or recurrent dermatitis. Treatments also include the following:

Corticosteroids: Topical corticosteroids are the mainstay of treatment, although acute, severe allergic contact dermatitis, such as from poison ivy, often needs to be treated with a 2-week course of systemic corticosteroids

Topical immunomodulators (TIMs): Approved for atopic dermatitis, but they are also prescribed for cases of allergic contact dermatitis when they offer safety advantages over topical corticosteroids

Phototherapy: Administered to individuals with chronic allergic contact dermatitis that is not controlled well by topical corticosteroids; these patients may benefit from treatment with a combination of psoralen (a photosensitizer) and ultraviolet-A (PUVA)

Immunosuppressive agents: Chronic immunosuppressive agents are, in rare instances, used to treat recalcitrant cases of severe, chronic, widespread allergic contact dermatitis or severe hand dermatitis that prevents a patient from working or performing daily activities

Disulfiram: Occasionally, an individual who is highly allergic to nickel and has severe vesicular hand dermatitis will benefit from treatment with disulfiram (Antabuse); the drug has a chelating effect

See Treatment and Medication for more detail.

Image library

Chronic stasis dermatitis with allergic contact dermatitis to quaternium-15, a preservative in moisturizer. Allergic contact dermatitis produces areas of erythema in areas of atrophie blanche and varicose veins.

BackgroundAllergic contact dermatitis (ACD) is a delayed type of induced sensitivity (allergy) resulting from cutaneous contact with a specific allergen to which the patient has developed a specific sensitivity. This allergic reaction causes inflammation of the skin manifested by varying degrees of erythema, edema, and vesiculation.

The term contact dermatitis sometimes is used incorrectly as a synonym for allergic contact dermatitis. Contact dermatitis is inflammation of the skin induced by chemicals that directly damage the skin (see Irritant Contact Dermatitis) and by specific sensitivity in the case of allergic contact dermatitis.

Jadassohn first described allergic contact dermatitis in 1895. He developed the patch test to identify the chemicals to which the patient was allergic. Sulzberger popularized patch testing in the United States in the 1930s. The Finn chamber method for patch testing was designed in the 1970s; these chambers consist of small metal cups, typically attached to strips of tape, filled with allergens dispersed in either petrolatum or water. The thin-layer rapid use epicutaneous (TRUE) test for patch testing became available in the United States in the 1990s.

The importance of specific substances as causes of allergic contact dermatitis varies with the prevalence of that substance in the environment. Mercury compounds once were significant causes of allergic contact dermatitis but rarely are used as topical medications and, currently, are uncommon as a cause of allergic contact dermatitis. Ethylenediamine, which was present in the original Mycolog cream, declined as a primary cause of allergic contact dermatitis once Mycolog cream was reformulated to no longer contain this allergen.

A detailed history, both before and after patch testing, is crucial in evaluating individuals with allergic contact dermatitis. Before patch testing, the history identifies potential causes of allergic contact dermatitis and the materials to which individuals are exposed that should be included in patch testing. After patch testing, the history determines the clinical significance of the findings. (See Clinical.)

Topical corticosteroids are the mainstay of treatment, while a variety of symptomatic treatments can provide short-term relief of pruritus. However, the definitive treatment of allergic contact dermatitis is the identification and removal of any potential causal agents; otherwise, the patient is at increased risk for chronic or recurrent dermatitis. (See Treatment.)

Go to Irritant Contact Dermatitis, Pediatric Contact Dermatitis, and Protein Contact Dermatitis for complete information on these topics.

PathophysiologyApproximately 3000 chemicals are well documented as specific causes of allergic contact dermatitis. Most of the chemicals able to provoke allergic contact dermatitis are small molecules (< 500 d). These molecules must bind to carrier proteins on Langerhans cells, which are situated within the suprabasilar layer of the epidermis.

Langerhans cells are the antigen-presenting cells within the skin. Langerhans cells interact with CD4+ T cells (helper T cells). Skin irritation by both nonallergenic and allergenic compounds induces Langerhans cell migration and maturation. In contrast, only allergenic compounds induce

CD1a+ CD83+ Langerhans cell migration with partial maturation at subtoxic concentrations.[2]

Cytokines also play an important role in allergic contact dermatitis because they regulate accessory-adhesion molecules, such as intercellular adhesion molecule 1. Interleukin 8 may be a cytokine indicating allergic contact dermatitis, not irritant contact dermatitis.

Langerhans cells can migrate from the epidermis to the regional draining lymph nodes. Sensitization to a chemical requires intact lymphatic pathways.

The initial sensitization typically takes 10-14 days from initial exposure to a strong contact allergen such as poison ivy. Some individuals develop specific sensitivity to allergens following years of chronic low-grade exposure; for example, sensitivity to chromate in cement can eventually develop in individuals with chronic irritant contact dermatitis resulting from the alkaline nature of cement. Once an individual is sensitized to a chemical, allergic contact dermatitis develops within hours to several days of exposure.

CD4+ CCR10+ memory T cells persist in the dermis after clinical resolution of allergic contact dermatitis.

Filaggrin barrier defects that predispose individuals to atopic dermatitis might also predispose them to allergic contact dermatitis by allowing greater penetration of chemical haptens.[3]

EtiologyApproximately 25 chemicals appear to be responsible for as many as one half of all cases of allergic contact dermatitis. These include nickel, preservatives, dyes, and fragrances.

Poison ivy

Poison ivy (Toxicodendron radicans) is the classic example of acute allergic contact dermatitis in North America. Allergic contact dermatitis from poison ivy is characterized by linear streaks of acute dermatitis that develop where plant parts have been in direct contact with the skin.

Nickel

Nickel is the leading cause of allergic contact dermatitis in the world. The incidence of nickel allergic contact dermatitis in North America is increasing; in contrast, new regulations in Europe have resulted in a decreasing prevalence of nickel allergy in young and middle-aged women.[4, 5]

Allergic contact dermatitis to nickel typically is manifested by dermatitis at the sites where earrings or necklaces (see the image below) containing nickel are worn or where metal objects (including the keypads of some cell phones[6] ) containing nickel are in contact with the skin.

Nickel may be considered a possible occupational allergen. Workers in whom nickel may be an occupational allergen primarily include hairdressers, retail clerks, caterers, domestic cleaners, and metalworkers. Individuals allergic to nickel occasionally may develop vesicles on the sides of the fingers (dyshidrotic hand eczema or pompholyx) from nickel in the diet.

Allergic contact dermatitis to nickel in a necklace.Rubber gloves

Allergy to 1 or more chemicals in rubber gloves is suggested in any individual with chronic hand dermatitis who wears them, unless patch testing demonstrates otherwise. Allergic contact dermatitis to chemicals in rubber gloves typically occurs maximally on the dorsal aspects of the hand. Usually, a cutoff of dermatitis occurs on the forearms where skin is no longer in contact with the gloves. Individuals allergic to chemicals in rubber gloves may develop dermatitis from other exposures to the chemicals (eg, under elastic waistbands).

Hair dye and temporary tattoos

p-Phenylenediamine (PPD) is a frequent component of and sensitizer in permanent hair dye products and temporary henna tattoos[7] ; exposure in to it in hair dye products may cause acute dermatitis with severe facial edema. Severe local reactions from PPD may occur in black henna tattoos in adults and children. Epidemiologic data indicate that the median prevalence of positive patch test reactions to PPD among dermatitis patients is 4.3% (increasing) in Asia, 4% (plateau) in Europe, and 6.2% (decreasing) in North America.[8]

Textiles

Individuals allergic to dyes and permanent press and wash-and-wear chemicals added to textiles typically develop dermatitis on the trunk, which occurs maximally on the lateral sides of the trunk but spares the vault of the axillae. Primary lesions may be small follicular papules or may be extensive plaques.

Individuals in whom this allergic contact dermatitis is suspected should be tested with a series of textile chemicals, particularly if routine patch testing reveals no allergy to formaldehyde. New clothing is most likely to provoke

allergic contact dermatitis, since most allergens decrease in concentration in clothing following repeated washings.

Preservatives

Preservative chemicals added to cosmetics, moisturizers, and topical medications are major causes of allergic contact dermatitis (see the image below). The risk of allergic contact dermatitis appears to be highest to quaternium-15, followed by allergic contact dermatitis to isothiazolinones (Kathon CG). Although parabens are among the most widely used preservatives, they are not a frequent cause of allergic contact dermatitis.

Severe allergic contact dermatitis resulting from preservatives in sunscreen. Patch testing was negative to the active ingredients in the sunscreen.Schnuch et al estimated that preservatives found in leave-on topical products varied over 2 orders of magnitude in relative sensitization risk.[9]

Formaldehyde is a major cause of allergic contact dermatitis (see the image below). Certain preservative chemicals widely used in shampoos, lotions, other moisturizers, and cosmetics are termed formaldehyde releasers (ie, quaternium-15 [Dowicil 200], imidazolidinyl urea [Germall 115], and isothiazolinones[9] ).

Onycholysis developing from allergic contact dermatitis to formaldehyde used to harden nails.Fragrances

Individuals may develop allergy to fragrances. Fragrances are found not only in perfumes, colognes, aftershaves, deodorants, and soaps, but also in numerous other products, often as a mask to camouflage an unpleasant odor. Unscented products may contain fragrance chemicals used as a component of the product and not labeled as fragrance.

Individuals allergic to fragrances should use fragrance-free products. Unfortunately, the exact chemicals responsible for a fragrance in a product are not labeled. Four thousand different fragrance molecules are available to formulate perfumes. The fragrance industry is not required to release the names of ingredients used to compose a fragrance in the United States, even when individuals develop allergic contact dermatitis to fragrances found in topical medications.

Deodorants may be the most common cause of allergic contact dermatitis to fragrances because they are applied to occlude skin that is often abraded by shaving in women.

Massage and physical therapists and geriatric nurses are at higher risk of

occupational allergic contact dermatitis to fragrances.

Corticosteroids

In the last decade, it has become clear that some individuals with chronic dermatitis develop allergy to topical corticosteroids. Most affected individuals can be treated with some topical corticosteroids, but an individual can be allergic to all topical and systemic corticosteroids. Budesonide and tixocortol pivalate are useful patch test corticosteroids for identifying individuals allergic to topical corticosteroids.

Neomycin

The risk of allergy to neomycin is related directly to the extent of its use in a population. The risk of allergy to neomycin is much higher when it is used to treat chronic stasis dermatitis and venous ulcers than when it is used as a topical antibiotic on cuts and abrasions in children. Assume that individuals allergic to neomycin are allergic to chemically related aminoglycoside antibiotics (eg, gentamicin, tobramycin).[10] Avoid these drugs both topically and systemically in individuals allergic to neomycin.

Benzocaine

Avoid topical use of benzocaine. Benzocaine is included in most standard patch test trays. Individuals allergic to benzocaine may safely use or be injected with lidocaine (Xylocaine), which does not cross-react with benzocaine.

Many individuals complain of adverse reactions to sunscreens, but many of these individuals are not allergic to the sunscreen materials. They may be allergic to preservatives in these products or may have nonspecific cutaneous irritation from these products.

Photoallergy

Occasionally, individuals develop photoallergic contact dermatitis. Allergic contact dermatitis may be accentuated by ultraviolet (UV) light, or patients may develop an allergic reaction only when a chemical is present on the skin and when the skin is exposed sufficiently to ultraviolet light A (UV-A; 320-400 nm).

EpidemiologyUnited States statistics

The National Health and Nutrition Examination Survey (NHANES) estimated the prevalence of contact dermatitis to be 13.6 cases per 1000 population, using physical examinations by dermatologists of a selected sample of patients. NHANES underreported the prevalence compared with the

physical examination findings.

The National Ambulatory Medical Care Survey conducted in 1995 estimated 8.4 million outpatient visits to American physicians for contact dermatitis. This was the second most frequent dermatologic diagnosis. Of office visits to dermatologists, 9% are for dermatitis. At a student health center dermatology clinic, 3.1% of patients presented for allergic contact dermatitis, and 2.3% presented for irritant contact dermatitis.

The TRUE test Web site can provide accurate basic information on common allergens. The Contact Allergen Management Program is provided as a service to the American Contact Dermatitis Society (ACDS) members and is particularly valuable for allergens found in topical skin care products. The Contact Allergen Replacement Database (CARD) contains more than 8100 known ingredients cataloged in more than 5500 commercial skincare products and is available as a Smartphone application.

International statistics

A Swedish study found that prevalence of allergic contact dermatitis of the hands was 2.7 cases per 1000 population. A Dutch study found that prevalence of allergic contact dermatitis of the hands was 12 cases per 1000 population.

Race, sex, and age-related demographics

No racial predilection exists for allergic contact dermatitis. Allergic contact dermatitis is more common in women than in men. This predominantly is a result of allergy to nickel, which is much more common in women than in men in most countries.

Allergic contact dermatitis may occur in neonates. In elderly individuals, the development of allergic contact dermatitis may be delayed somewhat, but the dermatitis may be more persistent once developed. Contact allergy to topical medicaments is more common in persons older than 70 years.[11]

PrognosisIndividuals with allergic contact dermatitis may have persistent or relapsing dermatitis, particularly if the material(s) to which they are allergic is not identified or if they continue to practice skin care that is no longer appropriate (ie, they continue to use harsh chemicals to wash their skin, they do not apply creams with ceramides or bland emollients to protect their skin).

The longer an individual has severe dermatitis, the longer it is believed it will take the dermatitis to resolve once the cause is identified.

Some individuals have persistent dermatitis following allergic contact dermatitis, which appears to be true especially in individuals allergic to chrome.

A particular problem is neurodermatitis (lichen simplex chronicus), in which individuals repeatedly rub or scratch an area initially affected by allergic contact dermatitis.

Mortality

Death from allergic contact dermatitis is rare in the United States. Allergic contact dermatitis to the weed wild feverfew caused deaths in India when the seeds contaminated wheat shipments to India. This plant then became widespread and a primary cause of severe airborne allergic contact dermatitis.

Patient EducationPatients have the best prognosis when they are able to remember the materials to which they are allergic and how to avoid further exposures. Provide patients with as much information as possible concerning the chemical to which they are allergic, including all known names of the chemical. Web sites, Smartphone applications, standard textbooks, and the TRUE test kit contain basic information about the chemicals.

Susceptible individuals need to read the list of ingredients before applying cosmetic products to their skin, since preservative chemicals are used widely in consumer, medical, and workplace products. The same chemical may have different names when used for consumer or industrial purposes.

Provide pamphlets with color pictures of poison ivy to individuals allergic to the plant. The American Academy of Dermatology also has pamphlets on allergic contact dermatitis and hand eczema.

For patient education information, see the Skin, Hair, and Nails Center, as well as Contact Dermatitis.

Proceed to Clinical Presentation

HistoryA detailed history, both before and after patch testing, is crucial in evaluating individuals with allergic contact dermatitis. Potential causes of allergic contact dermatitis and the materials to which individuals are exposed should be included in patch testing. Evaluation of allergic contact dermatitis requires a much more detailed history than most other dermatologic disorders.

History is equally important after patch testing. Only history and questioning can determine whether the materials to which a patient is allergic are partly or wholly responsible for the current dermatitis. A positive patch reaction may indicate only a sensitivity and not the cause of current dermatitis.

Preexisting skin diseases

Individuals with stasis dermatitis are at high risk for developing allergic contact dermatitis to materials and agents applied to the areas of stasis dermatitis and leg ulcers. Neomycin is an important cause of allergic contact dermatitis in these individuals because it is used frequently despite the lack of documentation of its efficacy in the treatment of stasis ulcers.

Individuals with otitis externa frequently are allergic to topical neomycin and topical corticosteroids.

Individuals with pruritus ani and pruritus vulvae may become sensitized to benzocaine and other medications applied to chronic pruritic processes.

Women with lichen sclerosus et atrophicus frequently develop allergic contact dermatitis, complicating the severe chronic vulvar dermatosis. Patch testing these patients may provide important information that can help in the management of recalcitrant and difficult-to-manage dermatosis.

Atopic dermatitis

Patients with a history of atopic dermatitis are at increased risk for developing nonspecific hand dermatitis and irritant contact dermatitis. However, they do not appear to be at an increased risk for allergic contact dermatitis, despite the wide range of topical medications and moisturizers used by individuals with chronic atopic dermatitis. They are at lower risk of allergic contact dermatitis to poison ivy. Some European studies indicate that patients with atopic dermatitis may have increased incidence of allergic contact dermatitis to nickel.

Onset of symptoms

Individuals with allergic contact dermatitis typically develop dermatitis, within a few days of exposure, in areas that were exposed directly to the allergen. Certain allergens (eg, neomycin) penetrate intact skin poorly, and the onset of dermatitis may be delayed up to a week following exposure.

A minimum of 10 days is required for individuals to develop specific sensitivity to a new contactant. For example, an individual who never has been sensitized to poison ivy may develop only a mild dermatitis 2 weeks following the initial exposure but typically develops severe dermatitis within 1-2 days of the second and subsequent exposures.

Remember that removing the poison ivy allergen from the skin is difficult, and unless an individual washes exposed skin within 30 minutes of exposure, allergic contact dermatitis will develop. The hallmark of the diagnosis of poison ivy is linear dermatitic lesions. The possibility of an external cause of dermatitis always must be considered if the dermatitis is linear or sharply defined.

The immediate onset of dermatitis following initial exposure to material suggests either a cross-sensitization reaction, prior forgotten exposure to the substance, or nonspecific irritant contact dermatitis provoked by the agent in question.

Eyelid dermatitis

Individuals may develop dermatitis on eyelids and other exposed skin following exposure to airborne allergens or allergens transferred to that site by the fingers. Contact dermatitis may also result from allergy to eyelid makeup.

Contact urticaria

Immediate reactions, ie, visible lesions developing less than 30 minutes after exposure, indicate contact urticaria (not allergic contact dermatitis). This is particularly true if the lesions are urticarial in appearance and if the skin reaction is associated with other symptoms, such as distant urticaria, wheezing, ophthalmedema, rhinorrhea, or anaphylaxis.

Latex

Rubber latex currently is the most important source of allergic contact urticaria (see Latex Allergy). The term hypoallergenic may refer to gloves that do not contain sensitizing chemicals added to rubber latex but may not indicate whether the gloves are rubber latex free.

Some individuals may have delayed specific contact sensitivity to rubber latex, but contact urticaria to rubber latex is much more common than allergic contact dermatitis to latex. Individuals with hand dermatitis, hospital workers, children with spina bifida, and atopic individuals are at increased risk of developing contact urticaria to rubber latex. Individuals may have allergic contact dermatitis to chemicals added to rubber gloves and have contact urticaria to latex. Individuals wearing rubber gloves should be evaluated carefully for both possibilities.

Rare reports exist of immediate anaphylactic reactions to topical antibiotics (eg, bacitracin).

Occupational dermatitis

Contact dermatitis is 1 of the 10 leading occupational illnesses. It may prevent individuals from working. The hands are the sites exposed most intensely to contact allergens and irritants, both at work and at home. Allergic contact dermatitis in response to workplace materials may improve initially on weekends and during holidays, but individuals with chronic dermatitis may not demonstrate the classic history of weekend and holiday improvement.

Irritant contact dermatitis is more likely if multiple workers are affected in the workplace. Most allergens rarely sensitize a high percentage of the population.

Hobbies

Hobbies may be the source of allergic contact dermatitis. Examples include woodworking with exotic tropical woods or processing film using color-developing chemicals that may provoke cutaneous lesions of lichen planus from direct skin exposure.

Medications

Medications (both self-prescribed and physician-prescribed) are important causes of allergic contact dermatitis. The workplace nurse may dispense ineffective and sensitizing topical preparations, such as thimerosal (Merthiolate), which may change a simple abrasion into a severe case of allergic contact dermatitis. Individuals may develop allergy to preservatives in medications and/or to the active ingredients in topical medications, especially neomycin and topical corticosteroids.[12, 13]

Patients with dermatitis that did not clear with topical corticosteroid treatment should be considered for patch testing with a corticosteroid series and the commercial preparations of corticosteroids and their vehicles.

Physical ExaminationAcute allergic contact dermatitis is characterized by pruritic papules and vesicles on an erythematous base. Lichenified pruritic plaques may indicate chronic allergic contact dermatitis. Occasionally, allergic contact dermatitis may affect the entire integument (ie, erythroderma, exfoliative dermatitis). The initial site of dermatitis often provides the best clue regarding the potential cause of allergic contact dermatitis. Note the following.

Hands

Hands are an important site of allergic contact dermatitis, particularly in the workplace. Common causes of allergic dermatitis on the hands include the chemicals in rubber gloves.

Topical medication sites

Allergic contact dermatitis is frequent in the perianal area as a result of the use of sensitizing medications and remedies (eg, topical benzocaine). Topical medications are also important causes of allergic contact dermatitis in cases of otitis externa. Allergy to chemicals in ophthalmologic preparations may provoke dermatitis around the eyes.

Airborne allergic contact dermatitis

Chemicals in the air may produce airborne allergic contact dermatitis. This dermatitis usually occurs maximally on the eyelids, but it may affect other areas exposed to chemicals in the air, particularly the head and the neck.

Hair dyes

Hair dye—in particular, the component p-phenylenediamine (PPD)—may trigger allergic contact dermatitis. Individuals allergic to hair dyes typically develop the most severe dermatitis on the ears and adjoining face rather than on the scalp.

Stasis dermatitis and stasis ulcers

Individuals with stasis dermatitis and stasis ulcers are at high risk for developing allergic contact dermatitis to topical medications applied to inflamed or ulcerated skin (see the image below). The chronicity of this condition and the frequent occlusion of applied medications contribute to the high risk of allergic contact dermatitis to medicament (eg, neomycin) in these patients.

Individuals may develop widespread dermatitis from topical medications applied to leg ulcers or from cross-reacting systemic medications administered intravenously. For example, a patient allergic to neomycin may develop systemic contact dermatitis if treated with intravenous gentamicin.

Chronic stasis dermatitis with allergic contact dermatitis to quaternium-15, a preservative in moisturizer. Allergic contact dermatitis produces areas of erythema in areas of atrophie blanche and varicose veins.Erythema multiforme

Erythema multiforme (EM) is a severe cutaneous reaction with targetoid lesions that occurs primarily after exposure to certain medications or is triggered by infection, most commonly by herpes simplex virus. Rare cases of EM have been reported after allergic contact dermatitis resulting from exposure to poison ivy,[14] tropical woods, nickel, and hair dye (see the image below).

Erythema multiformelike reaction that developed acutely following hair dying.Intraoral metal contact allergy may result in mucositis that mimics lichen planus, which has an association with intraoral squamous cell carcinoma. Intraoral squamous cell carcinoma adjacent to a dental restoration containing a metal to which the patient was allergic has been reported.[15]

Allergic contact dermatitis may be a direct trigger for skin ulceration in patients with venous insufficiency. Early diagnosis and treatment of allergic contact dermatitis may prevent the development of venous ulcers.

Complications

Darkly pigmented individuals may develop areas of hyperpigmentation or hypopigmentation from allergic contact dermatitis. Occasionally, they may develop depigmentation at sites of allergic contact dermatitis to certain chemicals.

Occasionally, allergic contact dermatitis is complicated by secondary bacterial infection, which may be treated by the appropriate systemic antibiotic.

Proceed to Differential Diagnoses

Diagnostic ConsiderationsContact dermatitis from allergy must be differentiated from contact dermatitis due to irritation, as well as other forms of dermatitis. In addition, the specific substance to which the patient is sensitive needs to be identified.

Differential DiagnosesAsteatotic EczemaContact Dermatitis, IrritantDrug-Induced Bullous DisordersDrug-Induced PhotosensitivityNummular DermatitisOnycholysisPerioral DermatitisPhytophotodermatitisPrurigo NodularisSeborrheic DermatitisTinea CorporisTransient Acantholytic DermatosisUrticaria, Contact Syndrome

Proceed to Workup

Approach Considerations

Guideline summaries are available as follows:

American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology -Allergy diagnostic testing: an updated practice parameter. Part 1 [16]

American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology -Allergy diagnostic testing: an updated practice parameter. Part 2 [17]

Go to Irritant Contact Dermatitis, Pediatric Contact Dermatitis, and Protein Contact Dermatitis for complete information on these topics.

Lab StudiesPotassium hydroxide preparation and/or fungal culture to exclude tinea are often indicated for dermatitis of the hands and feet. This will identify disorders such as tinea pedis.

Patch TestingPatch testing[18, 19, 20] is required to identify the external chemicals to which the person is allergic. The greatest quality-of-life benefits from patch testing occur in patients with recurrent or chronic allergic contact dermatitis (ACD). Patch testing is most cost-effective and reduces the cost of therapy in patients with severe allergic contact dermatitis.

Patch testing must be performed by health care providers trained in the proper technique. Most dermatologists can perform patch testing using the TRUE test, which can identify relevant allergies in as many as one half of affected patients. More extensive patch testing is indicated to identify allergies to chemicals not found in the TRUE test. Such testing typically is available only in a limited number of dermatology offices and clinics.

The patch testing procedure is as follows:

Small amounts of appropriate labeled dilutions of chemicals are applied to the skin and occluded for 2 days

Patch tests may be left on for 3 days before removalFor reasons of scheduling, a chemical must remain under a skin patch for a

minimum of 1 day to produce a positive patch test reaction 2-7 days following initial application

The patch test must be read not only at 48 hours, when the patch tests customarily are removed, but again between 72 hours and 1 week following initial application

Individuals with suspected allergic contact dermatitis without positive reactions on the TRUE test or with chronic dermatitis or relapsing dermatitis, despite avoiding chemicals to which they are allergic (identified

on TRUE test), need additional patch testing. Many individuals have more than 1 contact allergy and may be allergic to 1 or more chemicals found on the TRUE test and on special allergen trays or series.

Testing reactions to more allergens increases accuracy of the diagnosis of allergic contact dermatitis. Selection of allergens for testing requires consideration of the patient's history and access to appropriate environmental contactants.

Certain chemicals (eg, neomycin) typically produce delayed positive patch test reactions at 4 days or later following initial application. A tendency exists for elderly patients to manifest positive patch test reactions later than younger patients. Do not perform patch testing on patients taking more than 15 mg/d of prednisone. Oral antihistamines may be used during the patch test period if required.

Angry back syndrome or excited skin syndrome may occur. If a patient has a large number of positive patch test reactions, retesting the patient sequentially to a small series of these allergens may be necessary to exclude nonspecific false-positive reactions. The syndrome most likely occurs in individuals who have active dermatitis at the time of patch testing or who have a strong positive patch test reaction, both of which may induce local skin hyperreactivity in the area where patches were applied.

Additional patch test series or sets include the following:

Corticosteroids, particularly tixocortol pivalate and budesonideIngredients in cosmetics not found in the TRUE testChemicals used in dentistry that may produce mucosal and lip dermatitis in

dental clients or that may produce chronic dermatitis of the hands in dentists and dental team members

Chemicals used in hairdressing that may produce facial, ear, and neck dermatitis in clients or chronic hand dermatitis or eyelid dermatitis in hairdressers

Fragrances found in cosmetics and a wide range of consumer productsImportant allergens not found in the TRUE test that are frequent causes of allergic contact dermatitis are as follows:

BacitracinAcrylates used in dentistry, artificial nails, and printingChemicals used in bakingPesticides (many cases of dermatitis attributed to pesticides result from

other causes, particularly from plants such as poison ivy) Chemicals used in machining, eg, cutting oils and fluidsPhotographic chemicals used by photographers and photographic

developers

Plants excluding poison ivyChemicals in plastics and gluesChemicals found in rubber products not included in the TRUE testChemicals in shoes and clothingUltraviolet (UV) protective ingredients in sunscreensOther chemicals producing photo allergic contact dermatitisMiscellaneous allergensThe chemicals listed above are tested under Finn chambers, allergEAZE chambers, or the IQ Chamber patch test. In photopatch testing, the chemicals are applied in duplicate sets. One set receives 10 J/cm2 of UV-A (or 1 J/cm2 less than the minimum erythema dose, whichever is lowest) 24 hours after application of the allergens. The other series is protected from UV exposure to differentiate allergic contact dermatitis and photo-accentuated allergic contact dermatitis from photo-allergic contact dermatitis. Both sets are read at 48 hours after application, as well as at an additional time point as in routine patch testing.

The safety of patch testing in pregnancy has not been studied; however, the minute amounts of allergens applied appear unlikely to be absorbed in sufficient amounts to harm the fetus. Nonetheless, as with all treatments in pregnant women, the benefits of testing should be weighed against any potential, albeit undocumented, risk.

Repeat Open Application TestFor individuals who develop weak or 1+ positive reactions to a chemical, the repeat open application test (ROAT) is useful in determining whether the reaction is significant. ROAT is most useful when an individual has a 1+ reaction to a chemical found in a leave-on consumer product.

For example, an individual with a weak reaction to a preservative found in a moisturizer may apply the moisturizer twice a day for a week to the side of the neck or behind an ear; if clinical dermatitis does not develop, the 1+ reaction likely was not meaningful. Conversely, if dermatitis develops after a few days of repeated application of the suspected product, then the weak patch test reaction is highly relevant.

Dimethylgloxime TestThe dimethylgloxime test is a useful and practical way to identify metallic objects that contain enough nickel to provoke allergic dermatitis in individuals allergic to nickel. Dermatology staff may test suspected metal products in the office, or the individual may purchase a test kit and test objects at home or at work, particularly jewelry or metallic surfaces.

Other chemical tests are available for other suspected allergens (eg,

formaldehyde, cobalt, chromate). Occasionally, chemical analyses may be necessary to determine whether a material contains a suspected allergen or to identify new unknown allergens.

Skin BiopsySkin biopsy may help exclude other disorders, particularly tinea, psoriasis, and cutaneous lymphoma. Skin biopsy of skin lesions of the palms and soles has several potential pitfalls, however.

The stratum corneum and epidermis are particularly thick on the palms and soles. This makes the histologic diagnosis of psoriasis more difficult and increases the possibility that the biopsy specimen will lack sufficient dermis for optimal diagnosis.

An overly deep skin biopsy of the thenar area can cut the motor nerve, which is the recurrent branch of the median nerve. A biopsy from the sole may leave a chronic painful scar on which the patient must walk.

Histologic FindingsThe histology of allergic contact dermatitis is similar to that found in other forms of eczematous dermatitis. A pattern of subacute chronic dermatitis or acute dermatitis may be seen. The inflammatory infiltrate in the dermis predominately contains lymphocytes and other mononuclear cells.

Epidermal edema (ie, spongiosis and microvesicle formation) may be seen, but these changes may be absent in long-standing dermatitis in which thickening of the epidermis (acanthosis) with hyperkeratosis and parakeratosis may be seen in the epidermis and stratum corneum. Allergic contact dermatitis may provoke atypical T-cell infiltrates, simulating mycosis fungoides.

Proceed to Treatment & Management

BackgroundLeprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae. Leprosy can be considered 2 connected diseases that primarily affect superficial tissues, especially the skin and peripheral nerves. Initially, a mycobacterial infection causes a wide array of cellular immune responses. These immunologic events then elicit the second part of the disease, a peripheral neuropathy with potentially long-term consequences.

The social and psychological effects of leprosy, as well as its highly visible debilities and sequelae (as seen in the image below), have resulted in a

historical stigma associated with leprosy. To minimize the prejudice against those with leprosy, the condition is also known as Hansen disease, named after G.A. Hansen, who is credited with the 1873 discovery of M leprae. This mycobacterium grows extremely slowly and has not been successfully cultured in vitro.

Hands with Z-thumbs, clawing, contractures, and shortening of fingers due to repetitive injury and healing. Ho Chi Minh City, Vietnam. (Courtesy of D. Scott Smith, MD)In the 1990s, the World Health Organization (WHO) launched a campaign to eliminate leprosy as a public health problem by 2000. Elimination, as defined by the WHO, was defined as a reduction of patients with leprosy requiring multidrug therapy to fewer than 1 per 10,000 population. This goal was achieved in terms of global prevalence by 2002, but 15 of the 122 countries where leprosy was endemic in 1985 still have prevalence rates of greater than 1 per 10,000 population.[1]

Although multidrug regimens have been used globally to cure nearly 14 million patients with leprosy since 1985, the number of new leprosy cases remained relatively unchanged from 1980 to 2000, ranging from 500,000-700,000 worldwide per year.[2] Access and delivery of antibiotics continues to be a problem in the most endemic nations. With the precise transmission mechanism of leprosy still unknown and a lack of an effective vaccine, leprosy will probably continue to pose an ongoing public health problem in the coming decades.

PathophysiologyLeprosy can manifest in different forms, depending on the host response to the organism.

Individuals who have a vigorous cellular immune response to M leprae have the tuberculoid form of the disease that usually involves the skin and peripheral nerves. The number of skin lesions is limited, and they tend to be dry and hypoesthetic. Nerve involvement is usually asymmetric. This form of the disease is also referred to as paucibacillary leprosy because of the low number of bacteria in the skin lesions (ie, < 5 skin lesions, with absence of organisms on smear). Results of skin tests with antigen from killed organisms are positive in these individuals.

Individuals with minimal cellular immune response have the lepromatous form of the disease, which is characterized by extensive skin involvement. Skin lesions are often described as infiltrated nodules and plaques, and nerve involvement tends to be symmetric in distribution. The organism grows best at 27-30°C; therefore, skin lesions tend to develop in the cooler areas of the body, with sparing of the groin, axilla, and scalp. This form of

the disease is also referred to as multibacillary leprosy because of the large number of bacteria found in the lesions (ie, >6 lesions, with possible visualization of bacilli on smear). Results of skin tests with antigen from killed organisms are nonreactive.

Patients may also present with features of both categories; however, over time, they usually evolve to one or the other (indeterminate or borderline leprosy). Interestingly, most individuals who are exposed to leprosy never develop the disease.

Classification of leprosy: Leprosy has 2 classification schemas: the 5-category Ridley-Jopling system and the simpler and more commonly used WHO standard.

Ridley-Jopling: Depending on the host response to the organism, leprosy can manifest clinically along a spectrum bounded by the tuberculoid and lepromatous forms of the disease. Most patients fall into the intermediate classifications, which include borderline tuberculoid leprosy, midborderline leprosy, and borderline lepromatous leprosy. The classification of the disease typically changes as it evolves during its progression or management. The Ridley-Jopling system is used globally and forms the basis of clinical studies of leprosy. It may also be more useful in guiding treatment regimens and assessing risk of acute complications. Physical findings in each subtype are presented in the Clinical section.

WHO system: The WHO recommends classifying leprosy according to the number of lesions and the presence of bacilli on a skin smear. This method is useful in countries where biopsy analysis in unavailable.

Paucibacillary leprosy is characterized by 5 or fewer lesions with absence of organisms on smear. Paucibacillary leprosy generally includes the tuberculoid and borderline lepromatous categories from the Ridley-Jopling system.

Multibacillary leprosy is marked by 6 or more lesions with possible visualization of bacilli on smear. Lepromatous leprosy, borderline lepromatous leprosy, and midborderline leprosy on the Ridley-Jopling scale are included in the multibacillary leprosy category.

EpidemiologyFrequency

United StatesIn the United States, an average of 150 cases are diagnosed each year. In 2004, 69 new cases of leprosy were detected and 131 total persons were reported to have the disease, according to the WHO. Most cases of leprosy in the United States are found in immigrants, although endemic foci exist in

parts of Louisiana, Florida, and Texas along the Gulf of Mexico; in Mexican and Asian California populations; and in Spanish Americans in New York City. Around 85% of these detected leprosy cases involve patients who have lived in foreign countries, primarily Asia, Africa, and Latin America.[3]

Based on genetic analysis studies, wild armadillos and many patients with leprosy in the southern United States are infected with the same strain of M leprae.[4] Leprosy may be a zoonosis in the southern United States because armadillos are a large reservoir for this disease.

InternationalAccording to WHO figures, the global registered prevalence of leprosy at the start of 2005 was 286,063 cases. Global annual detection rates have declined from 2001 to 2004, when 763,262 and 407,791 new cases were reported, respectively. Leprosy is still deemed a public health problem in 9 countries: Angola, Brazil, Central African Republic, Democratic Republic of the Congo, India, Madagascar, Mozambique, Nepal, and the United Republic of Tanzania. These countries account for 84% of reported cases. Furthermore, more than 94% of new cases of leprosy in Latin America are reported in Brazil.[1]

Mortality/Morbidity

Leprosy is rarely fatal, and the primary consequence of infection is nerve impairment and debilitating sequelae. According to one study, 33-56% of newly diagnosed patients already displayed signs of impaired nerve function.[5] According to estimates, 3 million people who have completed multidrug therapy for leprosy have sustained disability due to nerve damage. Although both lepromatous leprosy and tuberculoid leprosy involve the skin and peripheral nerves, tuberculoid leprosy has more severe manifestations. Nerve involvement results in loss of sensory and motor function, which may lead to frequent trauma and amputation. The ulnar nerve is most commonly involved.

Damage in the following nerves is associated with characteristic impairments in leprosy:

Ulnar and median - Clawed handPosterior tibial - Plantar insensitivity and clawed toesCommon peroneal -Foot dropRadial cutaneous, facial, and greater auricular nerves (may also be

involved; as seen in the image below)Patient with facial nerve palsy and contractures of the hand. Daloa, Ivory Coast. (Courtesy of D. Scott Smith, MD)

Infiltration by bacteria may lead to destruction of nasal cartilage (lepromatous leprosy), ocular involvement, and diffuse thickening of

the skin. Advanced cases of leprosy involve the loss of eyebrows and lashes, but these deformities are less common today.

Worldwide, leprosy is considered the most common cause of crippling of the hand, which is caused by ulnar nerve involvement.[6] Peroneal nerve involvement can lead to foot drop, posterior tibial nerve involvement, and clawed toes.

Race

Leprosy was once endemic worldwide, and no racial predilection is known. In the late 1800s, the incidence of leprosy in northern Europe and North America dropped dramatically, and the disease is now reported primarily in tropical areas.

Sex

Leprosy is generally more common in males than in females, with a male-to-female ratio of 1.5:1. In some areas in Africa, the prevalence of leprosy among females is equal to or greater than that in males.[2]

Age

Leprosy can occur at any age, but, in developing countries, the age-specific incidence of leprosy peaks in children younger than 10 years, who account for 20% of leprosy cases. Leprosy is very rare in infants; however, they are at a relatively high risk of acquiring leprosy from the mother, especially in

cases of lepromatous leprosy or midborderline leprosy.History

SymptomsPainless skin patch accompanied by loss of sensation but not itchiness (Loss

of sensation is a feature of tuberculoid leprosy, unlike lepromatous leprosy, in which sensation is preserved.) Chronic insensate patch is seen in the mage below. Chronic insensate patch due to leprosy infection. Ho Chi Minh City, Vietnam. (Courtesy of D. Scott Smith, MD)

Loss of sensation or paresthesias where the affected peripheral nerves are distributed

Wasting and muscle weaknessFoot drop or clawed hands (may result from neuritic pain and rapid

peripheral nerve damage; as seen in the image below)Characteristic clawed hand deformity caused by ulnar involvement in leprosy. Daloa, Ivory Coast. (Courtesy of D. Scott Smith, MD)

Ulcerations on hands or feet (ulcer at the metatarsal head is seen in the image below)Chronic nonhealing ulcer at the metatarsal head resulting from loss of sensation in the feet. Karigiri, Tamil Nadu, India. (Courtesy of Tara Ramachandra)

Lagophthalmos, iridocyclitis, corneal ulceration, and/or secondary cataract due to nerve damage and direct bacillary skin or eye invasion[7]

Symptoms in reactionsType 1 (reversal) - Sudden onset of skin redness and new lesionsType 2 (erythema nodosum leprosum [ENL]; as seen in the image below) -

Many skin nodules, fever, redness of eyes, muscle pain, and joint pain Patient with erythema nodosum leprosum type 2 reaction several weeks after initiation of drug therapy. This photograph was taken after tendon release. Redwood City, California. (Courtesy of D. Scott Smith, MD)

Travel: Leprosy should be considered in anyone who has lived in the tropics or who has traveled for prolonged periods to endemic areas. Exposure: The incubation period of leprosy is long, ranging from a few months to 20-50 years. The mean incubation time is estimated to be 10 years for lepromatous leprosy and 4 years for tuberculoid leprosy. The organism's slow dividing time (once every 2 wk) contributes to the challenge of epidemiologically linking exposures to the development of disease. Because of immunologic reasons, only around 5-10% of the population is estimated to be susceptible to infection.

PhysicalThe cardinal signs of leprosy include hypoesthesia, skin lesions, and peripheral neuropathy. The first physical signs of leprosy are usually cutaneous. The subtype of leprosy often determines the degree of skin involvement.

Physical examination should include the following:Evaluation of skin lesionsCareful sensory and motor examinationPalpation of peripheral nerves for pain or enlargement, with particular

attention paid to the following locations:Elbows - Ulnar nerveWrist - Superficial radial cutaneous and median nervesPopliteal fossa - Common peroneal nerveNeck - Great auricular nerve

Physical findings in specific leprosy subtypes include the following:Tuberculoid leprosyThe initial lesion is often a sharply demarcated hypopigmented macule that

is ovoid, circular, or serpiginous. The lesions may be somewhat elevated with a dry scaly center and erythematous borders.

Common lesion sites include the buttocks, face, and extensor surfaces of limbs. The perineum, scalp, and axilla are not normally

involved because of the temperature differential in these zones, as predilection is toward cooler zones.

As the disease progresses, lesions tend to destroy the normal skin organs such as sweat glands and hair follicles.

Superficial nerves that lead from the lesions tend to enlarge and are sometimes palpable. The patient may experience severe neuropathic pain. Nerve involvement can also lead to trauma and muscle atrophy.

Lepromatous leprosyThis form is characterized by extensive bilaterally symmetric cutaneous

involvement, which can include macules, nodules, plaques, or papules. Multiple flat hypopigmented lesions are seen in the image below. Multiple flat hypopigmented lesions on shoulder and neck, suggestive of multibacillary leprosy. Note ulceration of hypothenar area of hand, indicative of ulnar neuropathy. Redwood City, California, United States. (Courtesy of D. Scott Smith, MD)

Unlike lesions in tuberculoid leprosy, those in lepromatous leprosy have poorly defined borders and raised and indurated centers. As in all forms of leprosy, lepromatous lesions are worst on cooler parts of the body. Common areas of involvement include the face, ears, wrists, elbows, buttocks, and knees.

Hoarseness, loss of eyebrows and eyelashes, and nasal collapse secondary to septa perforation may occur in advanced cases of disease. Involvement of the eye may include keratitis, glaucoma, or iridocyclitis as seen in the image below. Man with advanced deformities caused by unmanaged leprosy. Keratitis, loss of eyebrow, thickened skin, and typical hand impairments. Ho Chi Minh City, Vietnam. (Courtesy of D. Scott Smith, MD)

The leonine facies associated with leprosy develop as the disease progresses, and the facial skin becomes thickened and corrugated.

Axillary and inguinal adenopathy may develop, in addition to scarring of the testes and subsequent gynecomastia and sterility.

Nerve involvement in lepromatous leprosy is not as severe as in tuberculoid leprosy, since nerves, although visibly thickened and highly infected, still function reasonably well in early stages of the disease.

Borderline tuberculoid leprosy: The lesions are few or moderate and asymmetric with almost complete anesthesia. Peripheral nerves are often involved and thickened asymmetrically, and cutaneous nerves are sometimes enlarged.

Midborderline leprosy: The number of skin lesions is moderate, and they are asymmetrical and somewhat anesthetic. Peripheral nerves may be somewhat symmetrically enlarged, but cutaneous nerves are

not.Borderline lepromatous leprosy: Moderate to numerous slightly

asymmetrical skin lesions appear with minor or no anesthesia. Peripheral nerves are often enlarged symmetrically, but cutaneous nerves are not.

Indeterminate leprosy: Skin lesions are typically either hypopigmented or hyperpigmented macules or plaques. Patients may note that these lesions are anesthetic or paresthetic.

CausesM leprae is the causative agent associated with leprosy, which has been recognized as an infectious disease for the last 2 millennia. M leprae was discovered as the causative agent in 1873. The acid fast, gram-positive bacillus is an obligate intracellular organism with a predilection for Schwann cells and macrophages. M leprae has not been successfully grown using artificial media. The route of transmission has not been definitively established, although human-to-human aerosol spread of nasal secretions is thought to be the most likely mode of transmission in most cases. Leprosy is not spread by touch, since the mycobacteria are incapable of crossing intact skin. Living near people with leprosy is associated with increased transmission. Among household contacts, the relative risk for leprosy is increased 8- to 10-fold in multibacillary and 2- to 4-fold in paucibacillary forms. Animal reservoirs do exist (armadillos, certain nonhuman primates), and cases of suspected zoonotic transmission have been reported.

Proceed to Workup

Laboratory Studies

The WHO case definition of leprosy is M leprae infection in an individual who has not completed a course of treatment and has one or more of the following:

Hypopigmented or reddish skin lesions with loss of sensationInvolvement of the peripheral nerves as demonstrated by their thickening

and associated loss of sensationSkin smear positive for acid-fast bacilliLaboratory studies include the following:

Skin biopsy, nasal smears, or both are used to assess for acid-fast bacilli using Fite stain. Biopsies should be full dermal thickness taken from an edge of the lesion that appears most active.[8]

Serologic assays can be used to detect phenolic glycolipid-1 (specific for M leprae) and lipoarabinomannan (commonly seen in mycobacteria).[8]

Molecular probes detect 40-50% of cases missed on prior histologic evaluation. Since probes require a minimum amount of genetic material (ie, 104 DNA copies), they can fail to identify paucibacillary leprosy.

Laboratory tests related to drug treatment follow-up include the following:

CBC countCreatinine levelLiver function tests

Other TestsImmunologic tests include the following:

Lepromin skin test (not available in the United States): Although not diagnostic of exposure to or infection with M leprae, this test assesses a patient's ability to mount a granulomatous response against a skin injection of killed M leprae. Patients with tuberculoid leprosy or borderline lepromatous leprosy typically have a positive response (>5 mm). Patients with lepromatous leprosy typically have no response.

Phenolic glycolipid-1: This is a specific serologic test based on the detection of antibodies to phenolic glycolipid-1. This test yields a sensitivity of 95% for the detection of lepromatous leprosy but only 30% for tuberculoid leprosy.

Polymerase chain reaction (PCR): PCR and recombinant DNA technology have allowed for the development of gene probes with M leprae –specific sequences. This technology can be used to identify the mycobacterium in biopsy samples, skin and nasal smears, and blood and tissue sections.

Lymphocyte migration inhibition test (LMIT): As determined by a lymphocyte transformation and LMIT, cell-mediated immunity to M leprae is absent in patients with lepromatous leprosy but present in those with tuberculoid leprosy.

Contact or family screening for history of leprosy

ProceduresSkin biopsy samples stained with hematoxylin-eosin and Fite-Faraco are the primary basis for laboratory diagnosis and categorization. A full-thickness skin biopsy sample should be taken from an advancing border of an active lesion and should include dermis and epidermis. Skin smears that demonstrate acid-fast bacilli strongly suggest a diagnosis of leprosy, but the bacilli may not be demonstrable in tuberculoid (paucibacillary) leprosy. A nerve biopsy can be beneficial in ruling out diseases such as hereditary neuropathies or polyarteritis nodosa. Nerve biopsies may

also help identify abnormalities in patients with subclinical leprosy and may be the only way to definitively diagnose completely neuropathic forms of leprosy. If a nerve biopsy is needed to confirm diagnosis, a purely sensory nerve (eg, sural or radial cutaneous nerve) should be used. This procedure is rarely necessary.[7]

Histologic FindingsFindings vary but can include dermatitis, giant cells, infiltration of nerve bundles with mononuclear cells, and granulomas. Lepromatous lesions generally contain numerous acid-fast bacilli and fat-laden macrophages with a paucity of lymphocytes. Histopathology of leprosy is seen in the image below.

Histopathology of leprosy: Large numbers of acid-fast bacilli (in clusters) in histiocytes and within nerves. Fite-Faraco stain 500 X. (Courtesy of Tara Ramachandra and D. Scott Smith, MD)In contrast, tuberculoid lesions contain few-to-no acid-fast bacilli but manifest granulomatous changes with epithelial cells and lymphocytes. The immunopathologic spectrum of leprosy has been delineated in the Neurologic Manifestations of Leprosy topic in Medscape Reference's Neurology volume.

StagingLeprosy is staged or graded based on microscopy findings to classify cases as paucibacillary or multibacillary so that duration and type of drug therapy can be determined.

Proceed to Treatment & ManagementMedical CareIn response to the increased incidence of dapsone resistance, the WHO introduced a multidrug regimen in 1981 that includes rifampicin, dapsone, and clofazimine. Some clinical studies have also shown that certain quinolones, minocycline, and azithromycin have activity against M leprae. The WHO recently recommended single-dose treatment with rifampin, minocycline, or ofloxacin in patients with paucibacillary leprosy who have a single skin lesion. However, the WHO still recommends the use of the long-term multidrug regimens whenever possible because they have been found to be more efficacious.

Table. Multidrug Therapy Plan Recommended by the WHO (Open Table in a new window)

Type of LeprosyDaily, Self-Administered

Monthly Supervised

Months of Treatment

Paucibacillary Dapsone 100 mg Rifampicin 600 mg 6-12Multibacillary Dapsone 100 mg, Rifampicin 600 mg, 24

Clofazimine 50 mg Clofazimine 300 mg

Pediatric Dapsone 2 mg/kg,

Clofazimine 1 mg/kg

Rifampicin 10 mg/kg,

Clofazimine 6 mg/kg

Same as in adults

US regimens emphasize the use of rifampin, which is the most bactericidal drug used to treat leprosy. Although a single dose of 600 mg once monthly (the WHO standard) is considered bactericidal, treatment plans in the United States may include doses of 600 mg/day.

Paucibacillary leprosy should be treated for 6-12 months with dapsone 100 mg/day unsupervised plus rifampin 600 mg/month supervised. This regimen should be followed by treatment with dapsone as monotherapy for 3 years in patients with tuberculoid leprosy or 5 years in patients with borderline lepromatous leprosy.

Multibacillary leprosy should be treated for 24 months with dapsone 100 mg/day unsupervised, clofazimine 50 mg/day unsupervised, and rifampin 600 mg plus clofazimine 300 mg/month supervised.

Corticosteroids have been used to treat nerve damage associated with leprosy, but a recent review of 3 randomized controlled trials shows no significant long-term effect.[9] Prednisolone is believed to minimize pain and acute inflammation. The recommended initial dose is prednisolone 40 mg daily.

Observations of increasing resistance in patients treated for leprosy have been reported in Southeast Asia, notably in Vietnam.[10] The drug most commonly found to be resistant is dapsone, often in the context of prior exposure or treatment attempts with monotherapy. Although drug resistance is an ongoing concern, it is difficult to assess in this slow-growing organism. In a study of M leprae strains from South America, few of 230 strains subjected to molecular drug-susceptibility analysis were drug-resistant. Of the 230 strains, 3 were identified as clinically relapsing and were found to be resistant by genetic testing; 2 of the 3 were dapsone-resistant; and 1 was dapsone-resistant and rifampin-resistant using genetic testing for point mutation.[11]

Surgical CareThe goals of surgical treatment in patients with leprosy are to prevent further deterioration, to improve motor function, and, in some cases, to improve sensation. Preoperative requirements: First, a full sensory and motor appraisal

with functional and occupational assessment must be completed to determine the extent of damage. Additionally, patients must have completed the multidrug therapy and should have negative skin smear results. The patient should not use steroids a few months before surgery, and acute neuritis should not be evident. Stiffness of hands and feet should be minimized with preoperative therapy. Neural surgery

Attempts to restore autonomic function and sensation are rarely undertaken since little evidence shows that function is significantly regained. Draining of acute nerve abscesses and fascicular dissection can reduce the pressure on nerves and may improve sensation. In some cases, longitudinal epineurotomy may relieve some sensory loss. Considerable nerve function can be regained in the posterior tibial nerve with neurovascular decompression via release of the flexor retinaculum. Calcaneal bands can be slit to relieve distal compression of branches on the sole of the foot.

Nerve grafts may be of some benefit in patients with localized lesions. Neural surgery may also be indicated in patients with unremitting nerve pain.

Reconstruction and functional restoration[6]In leprosy management, the goal of most surgical procedures is to remedy

motor paralysis due to primary nerve impairment. Claw fingers and Z-thumbs caused by ulnar nerve paralysis are among the most common deformities. Clawed hands are repaired with arthrodesis or with a tendon transfer to 1 of 4 insertion sites on the finger: interosseus tendons, proximal phalanx, dorsal extensor expansion, or flexor sheath annular pulleys. The palmaris longus, flexor digitorum superficialis, extensor carpi radialis longus, and extensor indices are tendons that can be used for transfer. Tendon transfers are also used to repair abduction and opposition of the thumb, dorsiflexion of the foot, and flexion and extension of the metacarpophalangeal and proximal interphalangeal joints, respectively.

Contractures of the hand, such as the thumb web contracture, can be repaired with Z-plasty, and joint stability can be improved with tenodesis.

The constrictions caused by repetitive injury and healing in patients with leprosy can be treated with several methods. Possible treatment options include removal of the carpal tunnel roof, ulnar nerve transposition anteriorly, and epicondylectomy.

Procedures that limit hyperextension of the metacarpophalangeal joint or keep it in flexion are not indicated in the insensate hands of patients with leprosy, who suffer from continued weakness.

Amputation is a last resort and is reserved for cases of extremely diseased tissue.

Eye procedures: Loss of eyelid function may be treated with passing a strip from the temporalis muscle through the eyelid and connecting it to the inner canthus. Tarsorrhaphy may help narrow the opening of the eyelid, and canthoplasty reduces sagging of the eyelids. Cosmetic surgery: After the disease is controlled medically, the following cosmetic procedures may also be considered:

Nasal reconstructionRemoval of excess skinReplacement of eyebrows using transplants of scalp hairRemoval of breast tissue formation due to gynecomastia

ConsultationsConsultations may include an orthopedic surgeon, dermatologist, neurologist, and physical therapist, based on the needs of the individual patient. 

Medication SummaryThe goals of pharmacotherapy are to eradicate the infection, to prevent complications, and to reduce morbidity.

The multidrug therapy plan recommended by the WHO can be used to plan therapy based on the type of leprosy (paucibacillary or multibacillary) and whether it is supervised monthly or self-administered daily (see Medical Care).

Antimycobacterial AgentsClass Summary

These agents have bactericidal and bacteriostatic activity against mycobacteria.

View full drug informationDapsone (Avlosulfon) 

Bactericidal and bacteriostatic against mycobacteria; mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Part of a 2-drug regimen for treatment of paucibacillary leprosy; part of a 3-drug regimen for treatment of multibacillary leprosy.

View full drug informationRifampin (Rifadin, Rimactane) 

For use in combination with at least 1 other antituberculous drug; inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Most bactericidal drug used against M leprae. Cross-resistance may occur.

Treat for 6-9 mo or until 6 mo have elapsed from conversion to sputum-culture negativity.

Part of 2-drug regimen for treatment of paucibacillary leprosy; part of 3-drug regimen for treatment of multibacillary leprosy.

View full drug informationClofazimine (Lamprene) 

Inhibits mycobacterial growth, binds preferentially to mycobacterial DNA. Has antimicrobial properties, but mechanism of action is unknown. Part of 3-drug regimen for treatment of multibacillary leprosy.

View full drug informationMinocycline 

Used to treat leprosy in patients who cannot tolerate clofazimine.

Proceed to Follow-up

Further Outpatient CareThe WHO recommends that the monthly doses of rifampin be administered under direct observation during the visit.Monthly outpatient follow-up is recommended during treatment, although weekly visits may be necessary if the patient experiences a leprosy reaction. Follow-up laboratory studies during treatment include the following:

UrinalysesCBC countCreatinineLiver function tests

Yearly skin scrapings taken from the 3 or 4 most active lesions are recommended.Response to treatment

Successful treatment can result in flattening and elimination of nodules, papules, and plaques, as well as improved nerve function. Bacillary load is rarely a convenient method of assessing response to treatment. Noncompliance or drug resistance should be suspected if intact organisms are present after several months of treatment.

Once treatment is completed, the patient should be monitored for the next 5-10 years to evaluate for signs of relapse. To date, the relapse

rate following completion of multidrug therapy has been 1% for both types of leprosy. In such cases, new bacillus-positive lesions may develop and should be treated with a thorough US regimen that incorporates once-daily rifampin (see Treatment).

Patients who have been successfully treated occasionally develop reversal reactions and further neuropathy. If skin biopsy samples are bacillus-negative, these patients are deemed to have a reversal reaction (see Complications).

ComplicationsCareful attention to the development of reversal reactions during treatment and prompt and proper management will minimize long-term neurologic sequelae.

Type 1 reactionReversal reaction, or lepra type 1 reaction, is a delayed-type

hypersensitivity reaction that arises when borderline leprosy shifts toward borderline lepromatous leprosy with treatment. These types of reactions reflect the development of an appropriate immune response and the local generation of tumor necrosis factor-alpha and interferon-gamma. The reaction is characterized by edema and erythema of existing skin lesions, formation of new skin lesions, neuritis, and additional sensory and motor loss.

The likelihood of a type 1 reaction in patients with borderline leprosy is 30%.[7]

Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs) and high-dose steroids. Prednisone is given at a dose of 40-60 mg/day with a decreasing taper of 5 mg every 2-4 weeks after improvement is demonstrated.

Type 2 reactionErythema nodosum leprosum (ENL), also known as lepra type 2 reaction, is

a complication of lepromatous leprosy. It is characterized by the development of inflamed subcutaneous nodules accompanied at times by fever, lymphadenopathy, and arthralgias. High levels of tumor necrosis factor-alpha and immune complex deposition are associated with ENL.[7] Treatment includes prednisolone, clofazimine, or thalidomide. Erythema nodosum leprosum reaction is seen in the image below. Patient with multibacillary leprosy showing subsequent erythema nodosum leprosum reaction. Santa Clara, California. (Courtesy of D. Scott Smith, MD)

Mild ENL reactions are treated with aspirin 600-1200 mg/day in 4-6 doses per day.

Severe ENL reactions are treated with prednisone 60-80 mg/day with a slow taper, reducing by 5-10 mg every 2-4 weeks, depending on response and severity, to prevent residual deformity and nerve damage.

Alternatively, thalidomide 100 mg PO 4 times per day (if available and in the absence of contraindications) can be used in cases that involve large subcutaneous plaques, arthritis, and temperature that exceeds 38.8°C.

Lucio phenomenon is a severe complication of multibacillary leprosy that is marked by blue hemorrhagic plaques and necrotic ulcerations. The bacilli may extend to the endothelial cells along with the appearance of necrotic epidermis and vasculitis with thrombus formation and endothelial proliferation.

PrognosisRecovery from neurologic impairment is limited, but skin lesions generally clear within the first year of therapy. Discoloration and skin damage typically persist. Physical therapy, reconstructive surgery, nerve and tendon transplants, and surgical release of contractures have all contributed to increasing the functional ability in patients with leprosy. A common residual deformity is insensitive feet, as seen in persons with diabetes.

Patient EducationRegional ambulatory clinics: The National Hansen's Disease Programs (NHDP) provide outpatient services and medical care to patients with leprosy in the United States and Puerto Rico. With the goals of prevention and early detection, the program supports delivery of services in areas with considerable populations of patients with leprosy. For additional information about these free services, contact the NHDP directly at 1-800-642-2477. The NHDP Center in Baton Rouge, La, provides free histopathologic services to facilitate diagnosis. Eleven outpatient HD clinics are located at hospitals, universities, and public health departments in Arizona, California, Florida, Illinois, Massachusetts, New York, Puerto Rico, Texas, and Washington. These clinics provide the following services:

Skin biopsy diagnostic confirmationAdditional medical careHospitalization for treatment complicationsConsultationsMaterials for professional and patient education

Patients with leprosy should be advised about the importance of continuing long-term therapy until the course of antibiotics is

completed. The WHO recommends that the monthly administration of rifampin be directly observed. In patient with leprosy who have advanced nerve damage, self-care techniques are of utmost importance in maintaining function and preventing further disability. The use of visual input to regulate activity, self-inspection, hygiene, and proper footwear can help prevent ulcer formation and tissue damage. The WHO recommends examination of all household contacts of patients with leprosy, with careful instructions to seek medical care if signs and symptoms of leprosy appear.

Pregnancy in patients with leprosy can result in hormonal changes that lead to suppression of cell-mediated immunity, which may exacerbate symptoms of leprosy. Furthermore, pregnant women with leprosy are at greater risk of developing reactions and relapses. Type 1 reactions are more likely during the first few months following childbirth, whereas type 2 reactions typically occur during the third trimester of pregnancy and during lactation.[7]